Coronary calcium scans and radiation exposure in the multi-ethnic study of atherosclerosis

With the increasing use of coronary artery calcium (CAC) scoring to risk stratify asymptomatic patients for future cardiovascular events, there have been concerns raised regarding the theoretical risk of radiation exposure to this potentially large patient population. Newer CT protocols have sought to reduce radiation exposure without compromising image quality, but the reported radiation exposures in the literature remains widely variable (0.7–10.5 mSv). In this study, we report the radiation exposure of calcium scoring from our MESA cohort across several modern CT scanners with the aim of clarifying the radiation exposure of this imaging modality. To evaluate the mean effective doses of radiation, using dose length product, utilized for coronary artery calcium scoring in the MESA cohort, in an effort to understand estimated population quantity effective dose using individual measurements of scanner radiation output using current CT scanners. We reviewed effective dose in milliSieverts (mSv) for 3442 participants from the MESA cohort undergoing coronary artery calcium scoring, divided over six sites with four different modern CT scanners (Siemens64, Siemens Somatom Definition, GE64, and Toshiba 320). For effective dose calculation (milliSieverts, mSv), we multiplied the dose length product by conversion factor k (0.014). The mean effective dose amongst all participants was 1.05 mSv, a median dose of 0.95 mSV. The mean effective dose ranged from 0.74 to 1.26 across the six centers involved with the MESA cohort. The Siemens Somatom Definition scanner had effective dose of 0.53 (n = 123), Siemens 64 with 0.97 (n = 1684), GE 64 with 1.16 (n = 1219), and Toshiba 320 with 1.26 mSv (n = 416). Subgroup analysis by BMI, age, and gender showed no variability between scanners, gender, ages 45–74 years old, or BMI less than 30 kg/m². Subjects over age 75 yo had a mean effective dose of 1.29 ± 0.31 mSv, while the <75 yo subgroup was 0.78 ± 0.09 mSv (p < 0.05). Effective doses in subjects with BMI > 40 kg/m² was significantly greater than other subgroups, with mean dose of 1.47 ± 0.51 mSv (p < 0.01). Using contemporary CT scanners and protocols, the effective dose for coronary artery calcium is approximately 1 mSv, an estimate which is consistently lower than previously reported for CAC scanning, regardless of age, gender, and body mass index.     

The relationship between insulin resistance and incidence and progression of coronary artery calcification: the Multi-Ethnic Study of Atherosclerosis (MESA)

OBJECTIVE

We sought to determine whether insulin resistance predicts the incidence and progression of coronary artery calcification (CAC).

RESEARCH DESIGN AND METHODS

We studied 5,464 participants not on hypoglycemic therapy from the Multi-Ethnic Study of Atherosclerosis (MESA). Each had baseline homeostasis model assessment of insulin resistance (HOMA-IR) and baseline and follow-up CAC scores. Incident CAC was defined as newly detectable CAC; progression was defined as advancing CAC volume score at follow-up.

RESULTS

Median HOMA-IR was 1.2 (0.8–2.0). Across all ethnicities, there was a graded increase in CAC incidence and progression with increasing HOMA-IR. When compared with those in the 1st quartile, participants in the 2nd–4th quartiles had 1.2, 1.5, and 1.8 times greater risk of developing CAC. Median annualized CAC score progression was 8, 14, and 17 higher, respectively. However, HOMA-IR was not predictive after adjustment for metabolic syndrome components.

CONCLUSIONS

HOMA-IR predicts CAC incidence and progression, but not independently of metabolic syndrome.Sensitivity to insulin-mediated glucose uptake varies at least sixfold in the general healthy population, with variability attributable to genetic and behavioral factors (1–4). In the clinical setting, insulin resistance is commonly inferred via its adverse consequences, which include dysglycemia, hypertension, low HDL cholesterol (HDL-C), high triglycerides, and subclinical inflammation (collectively, the metabolic syndrome) (5).Insulin resistance and the metabolic syndrome have both been shown to be strongly associated with measures of subclinical atherosclerosis, including coronary artery calcification (CAC) (6,7). Consistent with these observations, prospective studies have demonstrated that insulin resistance and metabolic syndrome are independent predictors of cardiovascular events (8,9). However, the degree to which insulin resistance and metabolic syndrome are mutually independent predictors remains debated, with prior results mixed (7,10). We sought to determine whether insulin resistance prospectively predicts the onset and progression of CAC, independent of metabolic syndrome.     

Clinical course and long-term follow-up of patients receiving implantable cardioverter-defibrillators

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are increasingly used for primary and secondary prevention of sudden cardiac death. Defibrillators were introduced into clinical practice in 1980. Since that time, factors affecting long-term survival and the natural history of defibrillator patients have not been described. OBJECTIVES: The purpose of this study was to identify clinical predictors of long-term survival in patients receiving ICDs. METHODS: The prognostic value of several clinical variables on the likelihood of survival or appropriate ICD therapy in 1,382 consecutive patients receiving ICDs from 1980 to 2003 were evaluated. Data were collected at the time of device implantation, and follow-up was completed through March 2005. RESULTS: In 70 +/- 51 months of follow-up (range 0-282 months), 792 patients died and 421 patients received appropriate ICD therapy at least once. Age, left ventricular ejection fraction, New York Heart Association (NYHA) functional class, Charlson comorbidity index, and antiarrhythmic drug use correlated with mortality. beta-Blocker and angiotensin-converting enzyme inhibitor use was associated with improved survival. Only NYHA functional class correlated with ICD therapy. Patients free of shocks for the first 5 years after ICD implantation had continued risk of arrhythmia recurrence. CONCLUSION: The heart failure characteristics of patients predicted ICD shock probability and survival better than the arrhythmia characteristics or the underlying heart disease. Antiarrhythmic drug use was associated with increased mortality. Beta-blocker and angiotensin-converting enzyme inhibitor use was associated with improved survival. A measurable arrhythmic risk even after prolonged shock-free intervals indicates the need for continued ICD therapy in all patients with appropriate ICD indications.     

Framingham risk equation underestimates subclinical atherosclerosis risk in asymptomatic women

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death among American women. Currently, global risk assessment derived by Framingham risk equation (FRE) is used to identify women at increased risk for CHD. Electron-beam computed tomography (EBCT) derived coronary artery calcium (CAC) scores are validated markers for future CHD events among asymptomatic individuals. However, the adequacy of FRE for identifying asymptomatic women with CAC is unknown. METHODS AND RESULTS: We studied 2447 consecutive non-diabetic asymptomatic females (55 +/- 10 years). Based upon FRE, 90% were classified as low-risk (FRE < or = 9% 10-year risk of hard CHD events), 10% intermediate-risk (10-20%), and none were considered as high-risk (> 20%). Coronary artery calcium was present in 33%, whereas CAC > or = 100 and CAC > or = 400 were seen in 10 and 3% of women, respectively. Overall, 20% of women had age-gender derived > or = 75th percentile CAC. According to FRE, the majority (84%) of women with significant CAC > or = 75th percentile were classified as low-risk. Approximately half (45%) of low-risk women with > or = 2 CHD risk factors and a family history of premature CHD had significant CAC. CONCLUSION: Framingham risk equation frequently classifies women as being low-risk, even in the presence of significant CAC. Determination of CAC may provide incremental value to FRE in identifying asymptomatic women who will benefit from targeted preventative measures.     

Visualizing coronary calcium is associated with improvements in adherence to statin therapy

BACKGROUND: Many patients lack motivation to control cardiovascular risk factors and clinicians have long sought ways to activate apathetic patients. Despite significant and consistent data on the benefits of lipid-lowering agents to reduce cardiovascular events, adherence and utilization of these agents remains low. We evaluated whether visualization of coronary calcium would positively affect patients' adherence rates. METHODS: We evaluated patients who underwent electron beam tomography (EBT) coronary calcium evaluation at least 1 year prior with a survey questioning them about health behaviors. Patients filled out baseline and follow-up questionnaires relating to lifestyle modifications, including statin utilization, diet, exercise, tobacco cessation and vitamin/antioxidant utilization. RESULTS: The study population consisted of 505 individuals on statin therapy on baseline who were followed for a mean of 3 +/- 2 years. Overall the statin compliance was lowest (44%) among those with CAC score in the first quartile (0-30), whereas 91% of individuals with baseline CAC score in the fourth quartile (>or= 526) adhered to statin therapy. In multivariable analysis, after adjusting for cardiovascular risk factors, age, and gender, higher baseline CAC scores were strongly associated with adherence to statin therapy. CONCLUSIONS: In addition to risk stratification for the asymptomatic person, patients visualizing coronary artery calcium may improve utilization and adherence to lipid-lowering therapy. Outcome studies and randomized trials need to be done to quantify the true value and cost-effectiveness of this approach.     

Differential associations between blood biomarkers of inflammation, oxidation, and lipid metabolism with varying forms of coronary atherosclerotic plaque as quantified by coronary CT angiography

Although epidemiologic data link biomarkers of cardiovascular risk with incident and prevalent coronary artery disease, exact anatomic relationships between biomarkers and coronary atherosclerosis as measured by coronary CT angiography remain unclear. Patients with acute chest pain who ultimately had no evidence of acute coronary syndrome underwent contrast-enhanced 64-slice coronary CT angiography to determine presence, extent and composition of coronary atherosclerotic plaque. We determined the differences in levels of blood biomarkers measured at the time of the CT scan between different CT-based atherosclerotic plaque groups. Among 313 patients (mean age: 51.6 ± 11 years, 62% male) high-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-2 were associated with the extent of calcified plaque (P = 0.03 and P < 0.001), while hs-CRP and apolipoprotein A1 were associated with the extent of non-calcified plaque (P = 0.03 and P = 0.004; respectively). Despite a generally lower risk profile, subjects with exclusively non-calcified plaque had significantly higher levels of hs-CRP and oxidized low-density lipoprotein (P = 0.01 and P = 0.03; respectively) and lower levels of adiponectin (P = 0.03) when compared to subjects with calcified plaque (n = 130, 42%). Biomarkers reflecting inflammation, vascular remodeling, oxidation, and lipoprotein metabolism maybe associated with different patterns of coronary atherosclerosis as quantified by coronary CT angiography.     

Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease

OBJECTIVES: Inflammatory bowel disease (IBD), especially Crohn's disease (CD), probably results from failure to downregulate a chronic Th1 intestinal inflammatory process. Induction of a Th2 immune response by intestinal helminths diminishes Th1 responsiveness. This study evaluates the safety and effectiveness of helminthic ova in the treatment of active IBD. METHODS: We studied four patients with active CD and three with ulcerative colitis (UC). In an initial treatment and observation period, a single dose of 2500 live Trichuris suis eggs was given orally, and patients were followed every 2 wk for 12 wk. Baseline medications were continued at the same dose throughout the study. Safety was monitored by following the patients' clinical status and laboratory studies at regular intervals. Patients also were monitored regularly using the Crohn's Disease Activity Index, Simple Clinical Colitis Activity Index (SCCAI), and the Inflammatory Bowel Disease Quality of Life Index (IBDQ). To assess safety and efficacy with repetitive doses, two patients with CD and two with UC were given 2500 ova at 3-wk intervals as maintenance treatment using the same evaluation parameters. RESULTS: During the treatment and observation period, all patients improved clinically without any adverse clinical events or laboratory abnormalities. Three of the four patients with CD entered remission according to the Crohn's Disease Activity Index; the fourth patient experienced a clinical response (reduction of 151) but did not achieve remission. Patients with UC experienced a reduction of the Clinical Colitis Activity Index to 57% of baseline. According to the IBD Quality of Life Index, six of seven patients (86%) achieved remission. The benefit derived from the initial dose was temporary. In the maintenance period, multiple doses again caused no adverse effects and sustained clinical improvement in all patients treated every 3 wk for >28 wk. CONCLUSIONS: This open trial demonstrates that it is safe to administer eggs from the porcine whipworm, Trichuris suis, to patients with CD and UC. It also demonstrates improvement in the common clinical indices used to describe disease activity. The benefit was temporary in some patients with a single dose, but it could be prolonged with maintenance therapy every 3 wk. The study suggests that it is possible to downregulate aberrant intestinal inflammation in humans with helminths.     

Coronary Artery Diameter Related to Calcium Scores and Coronary Risk Factors as Measured with Multidetector Computed Tomography: A Substudy of the Accuracy Trial

Arterial remodeling, an early change of atherosclerosis, can cause dilated arterial diameter. We measured coronary artery diameter with use of noncontrast 64-slice multidetector computed tomography (MDCT), and studied its association with coronary artery calcium levels and traditional coronary risk factors.We included 140 patients from the ACCURACY trial whose noncontrast MDCT images showed measurable coronary arteries. Using 3 measurements of left main coronary artery (LMCA) and right coronary artery (RCA) diameters within 3 mm of the ostium, we associated the results with traditional coronary risk factors and calcium scores.The prevalence of LMCA and RCA calcium was 22% and 51%, respectively. Mean arterial diameters were 5.67 ± 1.18 mm (LMCA) and 4.66 ± 1.08 mm (RCA). Correlations for LMCA and RCA diameters in 50 randomly chosen patients were 0.91 and 0.93 (interobserver) and 0.98 and 0.93 (intraobserver). Adjusted odds ratios for the relationship of LMCA and RCA diameters to calcium in male versus female patients were 5.65 (95% confidence interval [CI], 2.78–11.5) and 4.35 (95% CI, 2.24–8.47), respectively. Adjusted ratios and 95% CIs for the association of larger RCA diameter with age, hypertension, and body mass index were 1.36 (1.00–1.86), 3.13 (1.26–7.78), and 1.60 (1.16–2.22), respectively.Arterial diameters were larger in women and patients with higher calcium levels, and body mass index and hypertension were predictors of larger RCA diameters. These findings suggest a link between arterial remodeling and the severity of atherosclerosis.Key words: Arteriosclerosis/complications/pathology, calcinosis/complications, coronary artery disease/etiology/pathology, coronary vessels/pathology/physiology, dilatation, pathologic/pathology, disease progression, models, cardiovascular, regression analysis, risk assessment, tomography, x-ray computed/methodsAn early change of atherosclerosis is arterial remodeling, which can result in dilated arterial diameter. In positive (expansive) arterial remodeling, luminal size is often preserved.^1–4 Conventional coronary angiography and myocardial perfusion imaging detect anatomically significant and hemodynamically relevant luminal stenosis, respectively, but perform less well in depicting atherosclerotic disease in its earlier stages when luminal integrity has not yet been compromised by positive vascular remodeling. Imaging studies of early culprit lesions in patients with acute coronary syndrome have revealed an association of echolucent plaque and positive remodeling with unstable clinical presentation.^5–7 Many studies of normal human coronary artery size have been conducted during postmortem examinations of the heart.^8–17 Investigators using intravascular ultrasonography, cardiac magnetic resonance, and cardiovascular computed tomography (CT) have suggested that coronary plaque rupture could occur in positively remodeled lesions.^18,19 Large positively remodeled lesions as predictors of plaque rupture are the subject of active research. Intravascular ultrasonography yields good views of coronary artery lumina and arterial walls and can help to reveal disease that is not angiographically evident; however, it is an invasive technique that is unsuitable as a screening procedure.^20–22 Coronary artery calcium (CAC), as evaluated by means of cardiovascular CT, is currently used as a surrogate marker of atherosclerosis.^23,24 In this study, we used noncontrast 64-slice multidetector computed tomography (MDCT) to measure coronary artery diameters in patients who had been referred for CAC scoring. We then used these measurements to study the relationship of increased coronary artery diameter to CAC and to traditional cardiovascular (CV) risk factors.     

The relationship between resting heart rate and incidence and progression of coronary artery calcification: The multi-ethnic study of atherosclerosis (MESA)

ObjectiveElevated resting heart rate has been independently associated with cardiovascular and all-cause mortality. The pathophysiological mechanisms by which this increased risk occurs are unclear. We hypothesized that elevated resting heart rate will be associated with increased development of atherosclerosis, as assessed by the incidence and progression of coronary artery calcium (CAC).MethodsThe Multi-Ethnic Study of Atherosclerosis is a prospective cohort study of participants free of clinical cardiovascular disease at entry. Among persons without CAC at baseline, the association between increasing clinical categories of heart rate (<60, 61–70, 71–80, >80 bpm) and CAC incidence was assessed by relative risk regression after adjusting for covariates. Among those with detectable CAC at baseline, progression of CAC was assessed using multivariable robust linear regression.ResultsOur study population consisted of 6004 individuals (62 ± 10 years, 48% males). Among 3079 individuals with no detectable CAC at baseline, 20% (n = 620) developed CAC. After adjusting for CVD risk factors, participants with a baseline resting heart rate >80 bpm had an increased risk of incident CAC as compared to those with a resting heart rate <60 (relative risk = 1.65, 95% CI = 1.02, 2.66). Among persons with CAC present at baseline, participants with a baseline resting heart rate >80 bpm had greater CAC score progression than those with a resting heart rate <60 (β = 17.10; 95% CI = 4.29, 29.85).ConclusionElevated resting heart rate, a well-described predictor of cardiovascular mortality with unclear mechanism, is associated with increased incidence and progression of coronary atherosclerosis among individuals free of CVD at baseline.